1. Field of the Invention
The present invention relates to a method of preventing preeclampsia, and more specifically, to administering resibufogenin in early pregnancy in order to prevent preeclampsia by preventing the advent of hypertension, proteinuria, and the development of intrauterine growth restriction.
2. Description of the Prior Art
Preeclampsia remains an important problem in pregnancy. It is the second leading cause of fetal wastage and maternal and fetal morbidity in the United States and abroad Pridjian G, Puschett J B. Preeclampsia. Part 1: clinical and pathophysiologic considerations. Obstet Gynecol Surv 2002; 57 (9):590-8. Hazards associated with the development of the hypertension and proteinuria which characterize the disorder include progression to eclampsia and the all too frequent eventuation of intrauterine growth restriction (IUGR). Not only does the latter condition compromise fetal survival Pridjian G, Puschett J B. Preeclampsia. Part 1: clinical and pathophysiologic considerations. Obstet Gynecol Surv 2002; 57 (9):590-8, but may affect those children who survive with medical problems in later life Libby G, Murphy D J, McEwan N F, et al. Pre-eclampsia and the later development of type 2 diabetes in mothers and their children: an intergenerational study from the Walker cohort. Diabetologia 2007; 50 (3):523-30. Thus, prevention of the syndrome would represent an important advance. Indeed, as is the case with many disorders, interfering in the pathogenetic process before lasting and irreversible anatomical and pathophysiological processes have gained a foothold, may represent the only truly successful therapy.
An important problem in the development of diagnostic and therapeutic stratagems in preeclampsia has been the relative dearth of animal models Conrad K D. Animal models of preeclampsia: do they exist? Fetal Med Rev 1 990; 2:7-88. This is especially true of those which address the early events in its pathogenesis. Evidence has accumulated which suggests that the pathophysiologic events which result in the clinical features of preeclampsia occur long before the latter become manifest Roberts J M, Pearson G, Cutler J, Lindheimer M. Summary of the NHLBI Working Group on research on hypertension during pregnancy. Hypertens 2003; 41:437-445. Most likely, these baleful events occur in the first trimester Pridjian G, Puschett J B. Preeclampsia. Part II: experimental and genetic considerations. Obstetrical and Gynecological Survey 2002; 57:619-640.
Pregnancy represents nature's experiment in the phenomenon of volume expansion. Pregnancy results in an increase in body volume of from 40 to 50% over baseline values as gestation proceeds Scott D E. Anemia in pregnancy. Obstet Gyn Ann 1972; 1:219-44. We have postulated that a segment of the preeclamptic population represents a group of patients whose expansion is excessive and who have an impaired ability to excrete excess salt and water because of a defect in sodium handling by the kidneys Puschett, J B. The role of excessive volume expansion in the pathogenesis of preeclampsia. Medical Hypotheses 2006; 67:1125-1132.
There remains a very real and substantial need for a method of preventing preeclampsia.